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At least 19 recordsLinked to original sources
PubMed1986

Anti-endothelial cell antibody and immune complexes in the sera of animals with acute experimental allergic encephalomyelitis and chronic relapsing experimental allergic encephalomyelitis.

Blood-brain barrier (BBB) injury occurs in both acute and chronic relapsing experimental allergic encephalomyelitis (EAE). Sera from animals in which these forms of EAE had been induced were examined for anti-endothelial cell antibodies and immune complexes by enzyme-linked immunosorbent assay (ELISA) using either cultured endothelial cells or Raji cells. IgG binding to endothelial cells was significantly increased in the sera of animals with acute EAE and chronic relapsing EAE, compared to controls. Increased levels of circulating immune complexes were also detected in the sera of some animals with chronic relapsing EAE, especially those in an exacerbation. It is suggested that the anti-endothelial cell antibody and immune complexes detected may play pathogenetic roles in the destruction of the BBB in EAE.

Animals↗
PubMed1975

Experimental autoimmune demyelinating diseases: experimental allergic encephalomyelitis and experimental allergic neuritis.

Experimental allergic encephalomyelitis (EAE) and experimental allergic neuritis (EAN) are reproducible models of auto-allergic demyelinating diseases of central and peripheral neurons tissue respectively. EAE bears a close resemblance to naturally-occuring post-infectious encephalomyelitis and EAN to Laundry-Guillain-Barré polyneuritis, in humans. In the experimental models the antigen responsible for disease induction is a different myelin basic protein in each disease. Although a variety of humoral antibodies to various neural fractions are found in both disorders, it has been shown that disease results from cell-mediated immune reactions to specific myelin antigens.

Autoantibodies↗
PubMed1998

A common immunoregulatory locus controls susceptibility to actively induced experimental allergic encephalomyelitis and experimental allergic orchitis in BALB/c mice.

Previous studies have shown that differential susceptibility to actively induced experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) exists among various BALB/c substrains. Of eight substrains studied for EAE and 13 for EAO, BALB/cJ mice are phenotypically the most resistant to disease induction. Resistance to both diseases is controlled by single recessive mutations unlinked to any of the known alleles distinguishing BALB/cJ mice. In this study, segregation analysis employing a second generation backcross population shows that resistance to both EAE and EAO is due to a mutation in a common immunoregulatory gene. The role of immunoregulatory cells in controlling EAE resistance was examined using adoptive transfer protocols. BALB/cJ mice immunized with spinal cord homogenate plus adjuvants generate immunoregulatory spleen cells (SpC) that, when transferred to naive BALB/cByJ recipients, reduce the incidence and severity of EAE. Treatment of such cells with either cytotoxic monoclonal anti-Thy1.2 or anti-CD4 plus C' before transfer abrogates the ability of BALB/cJ SpC to inhibit disease. In contrast, neither SpC from adjuvant-immunized BALB/cJ nor spinal cord homogenate- plus adjuvant-primed BALB/cByJ donors influences the incidence or severity of disease observed in recipients. In addition, the role of environment in influencing susceptibility to EAE and EAO in BALB/c mice is documented. Taken together, these results support the existence of a common disease susceptibility locus in the pathways leading to two autoantigenically distinct CD4+ T cell-mediated, organ-specific, autoimmune diseases.

Animals↗
PubMed1987

Differential susceptibility to actively induced experimental allergic encephalomyelitis and experimental allergic orchitis among BALB/c substrains.

Experimental allergic orchitis (EAO) and experimental allergic encephalomyelitis (EAE) are animal models of organ-specific autoimmune disease. In this study, BALB/cByJ and BALB/cAnNCr mice were susceptible to both autoimmune diseases whereas BALB/cJ subline mice were resistant. Disease resistance in BALB/cJ mice did not appear to be a reflection of either (i) a nonspecific generalized impairment of cellular immunity or (ii) an alteration in the phenotypic expression of Bordetella pertussis-induced histamine sensitization, a phenotype which has been shown to be associated with susceptibility to both diseases. Susceptibility to both EAE and EAO was inherited as a dominant trait in F1 hybrid animals. Segregation analysis in a (BALB/cByJ X BALB/cJ) X BALB/cJ backcross population suggested that disease resistance may be associated with a single genotypic difference in a common regulatory gene affecting susceptibility to both diseases. Linkage analysis of the backcross population failed to demonstrate an association of disease resistance with the mutant raf-1b allele carried by BALB/cJ mice. The results of these studies support previous observations that multiple genotypic differences may in fact exist in mice of the BALB/cJ subline and that such differences play a significant role in the genetic control of susceptibility to EAE and EAO.

Animals↗
PubMed1976

Effect of levan on the stages of development of experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis was induced in male guinea pigs of the N13 strain by inoculation of an emulsion of basic protein of myelin with complete Freund's adjuvant. The disease was also passively transferred to other animals of the same strain by i.p. injection of sensitized lymphocytes obtained from donors inoculated with the antigenic emulsion eight days previously. Daily administration of levan markedly reduced the incidence and severity of the disease in actively sensitized animals. Little, if any, effect was obtained by levan treatment of animals with the passively transferred disease. The findings indicate that the previously reported inhibitory effect of levan on the development of experimental allergic encephalomyelitis is probably due mainly to a derangement of the afferent path (stage of sensitization). Administration of levan also causes a depletion of lymphocytes in the lymph nodes and this may presumably also affect the efferent path.

Animals↗
PubMed1998

Early eosinophil infiltration into the optic nerve of mice with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis is a murine model of preclinical autoimmune disease that has pathologic similarities to multiple sclerosis (MS). Although CD4+ T cells have been shown to play a crucial role in the development of disease, we recently demonstrated a link between the development of paralysis and eosinophil infiltration into the spinal cord. As such, CD4+ cells may initiate disease, but eosinophils may be the actual effector cells responsible for causing damage to myelin and causing paralysis. Because MS patients sometimes experience early visual problems, ie, optic neuritis, we explored whether an early eosinophil infiltrate was also observed in the optic nerves of SJL mice after the passive transfer of encephalitogenic T cells. Seven days after the passive transfer of myelin basic protein (MBP)-reactive T cell blasts, we observed a significant infiltration of eosinophils into the optic nerves of the mice. This infiltration persisted during the early phases of paralysis, then declined to baseline values by the peak of limb paralysis on Day 10, and remained at baseline during the remission phase of the disease. Remyelination of optic nerves was observed at this time. These results suggest that eosinophil infiltration into the optic nerve is one of the earliest events occurring after the passive transfer of encephalitogenic T cells in murine experimental allergic encephalomyelitis.

Animals↗
PubMed1997

Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mice by adoptive transfer of MBP-reactive T cells in order to investigate the role of astrocytes in pathology. GFAP protein and mRNA expression (analyzed using semiquantitative Western blot and RT-PCR techniques) were upregulated in the spinal cord of mice, which had developed a complete paralysis of hind- and fore-limbs and tail (grade 4 EAE), thus establishing that reactive gliosis occurred under these experimental conditions. Within the same samples and using similar techniques, we found that glutamine synthetase (GS) and glutamate dehydrogenase (GDH) expression were dramatically reduced. These two astrocytic enzymes are responsible for degradation of glutamate, the most abundant excitatory neurotransmitter in the brain. Since elevated levels of glutamate may be neurotoxic, we propose that the decreased capacity of astrocytes to metabolize glutamate may contribute to EAE pathology.

Adoptive Transfer↗
PubMed2006

1,25 Dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease model of multiple sclerosis (MS). Vitamin D deficiency is commonly observed in MS patients and vitamin D supplements reduce the clinical symptoms of EAE and MS. Earlier studies have shown that in vivo treatment with vitamin D analogs ameliorates EAE in association with the inhibition of IL-12 production and Th1 differentiation. The mechanisms in the regulation of Th1 response by vitamin D in EAE/MS are, however, not known. We show that in vivo treatment of C57BL/6 and SJL/J mice (i.p.) with 100 ng of 1,25 dihydroxyvitamin D3, on every other day from Day 0-30, ameliorates EAE in association with the inhibition of IL-12 production and neural antigen-specific Th1 response. In vitro treatment with 1,25(OH)2D3 inhibited IFNgamma-induced tyrosine phosphorylation of STAT1, without affecting JAK2, in EOC-20 microglial cells. Treatment of activated T cells with 1,25(OH)2D3 also inhibited the IL-12-induced tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 in association with a decrease in T cell proliferation in vitro. These findings highlight the fact that vitamin D modulates JAK-STAT signaling pathway in IL-12/IFNgamma axis leading to Th1 differentiation and further suggest its use in the treatment of MS and other Th1 cell-mediated autoimmune diseases.

Animals↗
PubMed1995

Syngeneic bone marrow transplantation eliminates V beta 8.2 T lymphocytes from the spinal cord of Lewis rats with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), is a paralytic disease of the central nervous system (CNS) mediated by T-lymphocytes reactive to myelin basic protein (MBP). Lewis rats actively immunized with fragment 68 to 82 of guinea pig MBP develop a monophasic disease with spontaneous recovery. Lymphocyte recognition of the primary encephalitogenic sequence of MBP (fragment 68 to 82) is V beta 8.2 T cell receptor (TCR) skewed [1-3]. Lewis rats in clinical remission at 1 month and 3 months after spontaneous resolution of EAE retain V beta 8.2 T-lymphocytes in the CNS when analyzed by reverse transcriptase polymerase chain reaction or in situ hybridization. In contrast, 1 and 3 months after clinical remission from syngeneic bone marrow transplantation, V beta 8.2 T lymphocytes are absent from the CNS. During clinically active EAE and inflammatory breakdown of the blood-brain barrier, immune ablation and reconstitution with syngeneic bone marrow results in clinical tolerance of the new immune system to myelin.

Animals↗
PubMed2004

Changes in characteristics of rat skeletal muscle after experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) serves as an animal model for certain neuroinflammatory diseases of the central nervous system, in particular multiple sclerosis (MS). EAE is accompanied by transient weakness or paralysis of hind limbs. We have investigated the effect of partial and transient conduction failure in the central nervous system on skeletal muscle function. At approximately 2.5 days after development of maximal clinical signs, body and medial gastrocnemius muscle mass were lower (by approximately 21 and 33%, respectively; P < 0.05) in EAE rats compared with controls. Fiber cross-sectional area was lower by 40-50% in all fiber types. Maximal force and power were substantially lower (by 58% and 73%) in EAE rats, as was the force normalized for muscle mass (35%). However, no such weakness was found when lower stimulation frequencies were used. Generation of similar submaximal forces was attributable to a slower relaxation in EAE muscles. This advantage for the EAE muscles was lost during repeated exercise. While fatigability was similar, the difference in relaxation rate between EAE and control disappeared in fatigue. Our data suggest that, as a result of central neuroinflammatory diseases, maximal performance of skeletal muscle is impaired but submaximal performance is relatively well maintained.

Animals↗
PubMed1994

The distribution of inflammatory demyelinated lesions in the central nervous system of rats with antibody-augmented demyelinating experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) has long been studied as an animal model of the human demyelinating disease Multiple Sclerosis. However, EAE induced in the Lewis rat by injection of myelin basic protein (MBP), or MBP-specific T-lymphocytes, is primarily an inflammatory condition of the central nervous system (CNS) with little or no demyelination. In EAE models in which demyelination does result, it is either not very widespread or is unpredictable in its degree and location. In this study we have produced antibody-augmented demyelinating EAE (ADEAE) in the Lewis rat by injection of activated MBP-specific T-lymphoblasts, followed by injection 4 days later of a monoclonal antibody against myelin/oligodendrocyte glycoprotein, an extrinsic protein of myelin. We have documented the extent and location of inflammatory cell infiltrates and demyelination throughout the CNS using histochemistry, immunofluorescence, and image analysis. Perivascular inflammatory infiltrates were seen in the deep cerebellar white matter and in the folia. Perivascular, periventricular, and subpial inflammation was widespread throughout the pons/medulla and at all levels of the spinal cord. Very little inflammation was apparent in the forebrain. MBP immunofluorescence demonstrated extensive areas of periventricular demyelination in the forebrain around the third ventricle. Both periventricular and perivascular lesions were commonly observed in the cerebellum and pons/medulla. The extent of demyelination in the spinal cord increased caudally with large confluent areas of subpial demyelination seen throughout the lumbar cord. The extensive and reproducible distribution of inflammatory demyelinating lesions in ADEAE provide the possibility to select areas of the CNS for more detailed analysis of the cellular changes that accompany demyelination and remyelination.

Animals↗
PubMedDate not supplied

Modulation of Outward K(+) Conductance Is a Post-Activational Event in Rat T Lymphocytes Responsible for the Adoptive Transfer of Experimental Allergic Encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is an accepted animal model for the human demyelinating disease multiple sclerosis. The continuously propagated line of Lewis rat T helper lymphocytes (GP1 T cells), specific for the encephalitogenic 68-86 sequence of guinea pig myelin basic protein (GPMBP), mediates the adoptive transfer of EAE into normal syngeneic Lewis rats. Because mitogenic activation of T cells can increase K(+) conductance, this study investigated changes in the outwardly rectifying K(+) conductance in GP1 T cells following activation with the encephalitogen, GPMBP. Using the gigohm.seal whole-cell variation of the patch clamp technique, GP1 T cells were studied during a 3-day culture with GPMBP and throughout the subsequent 10 days, as cells progressed through both GPMBP-induced activation (EAE transfer activity) and proliferation responses, finally reverting to the resting state. Resting GP1 T cells exhibited peak K(+) conductances around 2 nS, while GPMBP-induced activation resulted in 5- to 10-fold increases in peak K(+) conductance, which temporally coincided with the optimal period for EAE transfer activity. During and immediately after the optimal period for EAE transfer, 20-mV depolarizing shifts in the voltage dependence of both activation and inactivation developed, abruptly reversing to resting values as cells reverted to the resting state. Accompanying the depolarizing shifts were a slowing of the K(+) current activation kinetics and an acceleration of the deactivation kinetics. These results indicate that the K(+) conductance in GP1 rat T helper cells is modulated over the full time course of GPMBP-induced cellular responses and that K(+) channels should be optimally available during the period of adoptive EAE transfer, preceding disease manifestation. Copyright 1997 S. Karger AG, Basel

Journal Article↗
PubMed2006

COX-2 inhibitors modulate IL-12 signaling through JAK-STAT pathway leading to Th1 response in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease model of multiple sclerosis (MS). IL-12 plays a crucial role in the pathogenesis of EAE/MS and inhibition of IL-12 production or IL-12 signaling was effective in preventing EAE. Cyclooxygenase (COX-2) is a key enzyme promoting inflammation in rheumatoid arthritis and tumor induced angiogenesis. Recent studies have shown that COX-2 inhibitors prevent EAE, however, their mechanism of action is not fully understood. In this study, we show that in vivo treatment (i.p.) with 100 mug COX-2 selective inhibitors (LM01, LM08, LM11, and NS398), on every other day from day 0 to 30, significantly reduced the incidence and severity of EAE in SJL/J and C57BL/6 mice. Further analyses showed that the COX-2 inhibitors reduced neural antigen-induced IL-12 production, T cell proliferation and Th1 differentiation ex vivo and in vitro. The COX-2 inhibitors also decreased IL-12-induced T cell responses through blocking tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 proteins in T cells. These results demonstrate that COX-2 inhibitors ameliorate EAE in association with the modulation of IL-12 signaling through JAK-STAT pathway leading to Th1 differentiation and suggest their use in the treatment of MS and other Th1 cell-mediated autoimmune diseases.

Animals↗
PubMed1975

Spinal and spino-bulbo-spinal reflexes in rats with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) often produces complete hindlimb paralysis in rats. Stimulating the dorsal root at L5 was found to produce hindleg twitches in EAE rats with complete hindlimb paralysis. In addition, it was possible to record a monosynaptic response from the ventral root at L5 after stimulating the ipsilateral dorsal root (L5) in these rats. It was also possible to elicit a reflex at L5 which was shown to involve the central nervous system above the spinal cord level. These experiments demonstrated that the motoneurons and the muscles of the hindlimbs and the spinal cord segment innervating the hindlimbs remain functional in EAE paralyzed rats. This suggests that the paralysis may be caused by dysfunction of descending pathways of supraspinal origin.

Animals↗
PubMedDate not supplied

Changes in the effectiveness of the blood-brain and blood-spinal cord barriers in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) was induced In Lewis rats by the intradermal inoculation of an homogenate of guinea pig spinal cord in complete Freund's adjuvant. In these animals the effectiveness with which the capillary barrier excluded mannitol (a substance which normally only crosses this barrier very slowly) from the brain and spinal cord involvement were at their height, 14 days after the inoculation, the effectiveness of the barrier was reduced since the rate of diffusion of the mannitol out of the blood into the brain-stem and spinal cord was approximately doubled. Even as early as 7 days after inoculation, before any clinical signs had appeared, the rate of diffusion was significantly increased in the region of the lumbo-sacral cord. These changes roughly paralleled the histological changes seen in many of the small vessels. We believe that the changes are due to an increase in the permeability of the vessels to mannitol. The bearing of these findings on multiple sclerosis is discussed.

Animals↗
PubMed1988

Increased blood concentration of des-Arg9-bradykinin in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is a delayed cell-mediated autoimmune reaction to myelin basic protein. The neuropathology of this acute inflammatory process is characterized by cellular infiltration of the perivascular nervous parenchyma which increases the blood-brain barrier permeability. There is good evidence for an activation of the kallikrein-kinin system during inflammation. In order to assess blood concentrations of kinins in a group of 21 New Zealand rabbits in the acute phase of EAE and a group of 12 normal controls, we performed a sensitive and specific radioimmunoassay. All subjects in the encephalomyelitic group were inoculated with 0.05 ml of an antigenic preparation. They all developed neurological deficits on average 30 days later and within 4 days 10 ml of arterial blood were withdrawn for radioimmunoassay of kinins. On the same days their central nervous system was dissected and prepared for staining and histological study. We demonstrated a significant difference in bradykinin blood concentration between the encephalomyelitic (170.6 pg/ml) and the control (245.8 pg/ml) groups. There is also a significant difference in des-Arg9-bradykinin blood concentration between the encephalomyelitic (168.0 pg/ml) and the control (96.1 pg/ml) groups. These results suggest an activation of circulating carboxypeptidases involved in the transformation of bradykinin into des-Arg9-bradykinin during EAE.

Animals↗